When asleep or under anesthesia, part of the human brain behaves as if it is remembering something, researchers from UCLA reported in the journal Nature Neuroscience.

The authors said that their findings go against conventional theories regarding how memory is consolidated while we sleep.

Team leader, Mayank R. Mehta, a professor of neurophysics in UCLA’s departments of neurology, neurobiology, physics and astronomy, and colleagues measured several parts of the brain known to be involved in memory formation for neural activity – all the multiple brain regions were measured for activity at the same time. By doing this, they were able to find out which region in the brain was activating other areas, as well as how exactly that activation was spreading.

Researchers from Heidelberg University in Germany, and the Max Planck Institute for Medical Research, and James McFarland of Brown University, were also involved in this study.

The animal experiment, which was done on mice, focused on three connected brain regions:

  • The neocortex (new brain)
  • The hippocampus (old brain)
  • The entorhinal cortex – an intermediate brain area that connect the two parts mentioned above

Mehta explained that prior studies had pointed towards a dialogue occurring between the new and old brain while people are asleep, which was said to be vital for memory formation. However, nobody had tried to determine what the contribution of the entorhinal cortex might be to this dialogue, which “turned out to be a game changer”.

The scientists discovered that the entorhinal cortex showed “persistent activity”, which experts say mediates working memory while we are awake, as may occur when we focus carefully in order to remember things for a short time, such as a phone number or to follow directions we have just read on a map.

Mehta said “The big surprise here is that this kind of persistent activity is happening during sleep, pretty much all the time. These results are entirely novel and surprising. In fact, this working memory-like persistent activity occurred in the entorhinal cortex even under anesthesia.”

We spend one third of our time sleeping, Mehta explained, thus their findings are important – sleep deprivation has a detrimental effect on health, including learning and memory.

Previous studies had shown that the hippocampus and neocortex “talk” to each other while we are asleep. Experts believe that this dialogue is a major contributor to our formation of memories or memory consultation. However, interpreting this dialogue between the two brain areas was never done.

Mehta explained:

“When you go to sleep, you can make the room dark and quiet and although there is no sensory input, the brain is still very active. We wanted to know why this was happening and what different parts of the brain were saying to each other.”

For this study, the researchers had managed to develop a highly sensitive monitoring system which helped them follow neuronal activity in each of the three brain areas at the same time, including the activity of a singly neuron.

Their monitoring was so sensitive that they could decipher the precise communications, even when the neurons appeared to be relatively quiet. With the help of a sophisticated mathematical analysis, they were able to decipher the complex conversations.

The neocortex spends 90% of our sleeping time in a slow wave pattern. Activity fluctuates slowly between active and dormant states, approximately once every second. The researchers focused on the brain area that has many parts; the entorhinal cortex.

Neocortical activity was mirrored in the outer part of the entorhinal cortex, but the inner part of the entorhinal cortex behaved differently. The neurons remained in their active state in the inner entorhinal cortex, even when the outer part went quiet – “as if the neurons were remembering something the neocortex had recently said”. The scientists called this phenomenon “spontaneously persistent activity”. Furthermore, this spontaneous persistent activity made the neurons in the hippocampus become very active too.

The hippocampus became quieter when the neocortex was active, however. The data the scientists collected provided them with a clear interpretation of how the “dialogue” between the different brain parts occurred.

Mehta said:

“During sleep the three parts of the brain are talking to each other in a very complex way. The entorhinal neurons showed persistent activity, behaving as if they were remembering something even under anesthesia when the mice could not feel or smell or hear anything. Remarkably, this persistent activity sometimes lasted for more than a minute, a huge timescale in brain activity, which generally changes on a scale of one thousandth of a second.”

Theories have supposed that the hippocampus talks to and drives the neocortex – this study challenges this. Instead, it indicates that there is a third key player in this complex dialogue – the entorhinal cortex, and that the neocortex drives the entorhinal cortex, which in turn appears to behave as if it were recalling something. This, in turn, seems to drive the hippocampus, while other activity patterns shut it down.

Mehta commented:

“This is a whole new way of thinking about memory consolidation theory. We found there is a new player involved in this process and it’s having an enormous impact. And what that third player is doing is being driven by the neocortex, not the hippocampus. This suggests that whatever is happening during sleep is not happening the way we thought it was. There are more players involved so the dialogue is far more complex, and the direction of the communication is the opposite of what was thought.”

Mehta believes that this process, which occurs while we are sleeping, is a way of getting rid of junk – deleting cluttered up and useless memories and erasing irrelevant data that was processed and gathered during the day.

This “decluttering” process results in relevant and important memories becoming more prominent and easier to access. Alzheimer’s disease commences in the entorhinal cortex. Alzheimer’s patients have impaired sleep. Mehta and team believe their findings may have implications in that area.

Mehta and colleagues plan to carry on with this research and try to uncover what mechanisms there are behind the brain activities they discovered, and to determine whether such activities might impact on subsequent behavioral performance.

The authors wrote:

“These results provide the first direct evidence for persistent activity in medial entorhinal cortex layer neurons in vivo, and reveal its contribution to cortico-hippocampal interactions, which could be involved in working memory and learning of long behavioral sequences during behavior, and memory consolidation during sleep.”

Written by Christian Nordqvist